MCL Literature Feed

This review highlights BTK's non-catalytic scaffolding function as a novel mechanism of BTKi resistance, presenting a new therapeutic target beyond kinase inhibition for treating B-cell lymphomas like MCL.

BTK inhibition suppresses key metabolic pathways, allowing non-invasive imaging of metabolites like lactate and alanine as early, sensitive biomarkers of therapeutic response in MCL patients.

A computational virtual screen of over 2.4 million compounds identified novel covalent BTK inhibitors, providing a foundation for developing next-generation therapeutics for MCL.

The dual HCK/BTK inhibitor KIN-8194 preclinically overcomes primary and acquired BTKi resistance in MCL by targeting HCK-mediated growth and adhesion, offering a novel therapeutic strategy.

The CDK9 inhibitor enitociclib overcomes resistance to both BTK inhibitors and CAR-T therapy, offering a potential new strategy for double-refractory mantle cell lymphoma.

An 85-year-old MCL patient on ibrutinib developed a cutaneous EBV+ NK/T-cell lymphoma that resolved spontaneously, highlighting a rare, potentially indolent lymphoproliferative disorder in this treatment setting.

The non-covalent BTK inhibitor pirtobrutinib demonstrates efficacy in mantle cell lymphoma patients who have progressed on prior covalent BTKi therapy, overcoming a common resistance mechanism.

This case report demonstrates delayed Hepatitis B reactivation with acalabrutinib in relapsed MCL, underscoring the need for viral screening and prophylaxis with second-generation BTK inhibitors.

In young, newly diagnosed MCL, first-line rituximab, bendamustine, and cytarabine (R-BAP) plus a BTK inhibitor improved complete response and PFS over standard R-CHOP/R-DHAP in a real-world setting.

In young, newly diagnosed MCL patients, adding ibrutinib to chemoimmunotherapy improves failure-free survival, establishing a new standard and questioning the necessity of autologous stem cell transplant consolidation.

The phase 3 TRIANGLE trial established that adding ibrutinib to induction/maintenance allows omission of autologous transplant in young, fit MCL patients, providing a new frontline, transplant-free standard.

This review summarizes the clinical data and rationale for targeted agents like BTK and BCL2 inhibitors, highlighting the paradigm shift away from chemotherapy in both relapsed/refractory and frontline MCL.

Transformed MCL with triple-hit genetics (MYC/BCL2/BCL6 rearrangements) can be resistant to BTK inhibitors, identifying a novel genomic mechanism of treatment failure in this aggressive setting.

This preclinical study elucidates acalabrutinib's metabolic pathways, identifying reactive intermediates that may explain potential drug-drug interactions, toxicities, or off-target effects in patients with MCL.

This review details the evolution of BTK inhibitors, highlighting improved toxicity with newer agents and the emergence of non-covalent BTKis and novel resistance mutations, impacting MCL treatment sequencing.

This phase 1/2 trial establishes the safety and efficacy of the BTKi acalabrutinib in Chinese patients with relapsed/refractory MCL, supporting its use in this specific population.

This commentary discusses the zandelisib (PI3Ki) plus zanubrutinib (BTKi) combination, suggesting a potential role for newer, potentially less toxic PI3K inhibitors in relapsed/refractory MCL.

In a European compassionate use program, pirtobrutinib demonstrated a 67% overall response rate and good safety in heavily pretreated, BTKi-exposed relapsed/refractory MCL, supporting its real-world clinical utility.

Brexucabtagene autoleucel (CAR-T) combined with BTK inhibitors is a potentially safe and effective strategy for treating relapsed mantle cell lymphoma with central nervous system involvement.

Combining CAR-T therapy with a BTK inhibitor may offer a synergistic strategy to effectively treat mantle cell lymphoma with central nervous system involvement, a historically poor-prognosis population.

An indirect comparison suggests brexucabtagene autoleucel provides superior response rates and progression-free survival over pirtobrutinib for MCL patients who have failed a prior covalent BTKi.

The PI3Ki zandelisib plus BTKi zanubrutinib combination shows high efficacy (74% ORR, 47% CR) with manageable toxicity in relapsed/refractory MCL, offering a promising chemotherapy-free regimen.

This preclinical study identifies DNMT3A-mediated metabolic reprogramming to oxidative phosphorylation as a novel ibrutinib resistance mechanism, which can be overcome by low-dose decitabine.

This review, while focused on CLL, details the metabolic and toxicity profiles of covalent and non-covalent BTKis, informing MCL management strategies for adverse events and emerging resistance.

Phospho-flow cytometry reveals that high constitutive AKT and inducible STAT5/SYK B-cell receptor signaling activity predicts shorter survival and ibrutinib resistance, offering a functional biomarker for high-risk MCL.

Real-world UK data show first-line ibrutinib is effective and tolerable for older MCL patients, but high-risk subgroups (TP53-mutated, blastoid) have significantly inferior survival, highlighting an unmet need.

This review details BTK inhibitor resistance mechanisms, particularly C481S mutations, and highlights non-covalent BTKi (pirtobrutinib) and PROTACs as key strategies to overcome relapse in MCL.

Combining time-limited ibrutinib with CTL019 CAR-T in relapsed/refractory MCL achieved an 80% CR rate with manageable toxicity, showing efficacy even in BTKi-pretreated and TP53-mutated patients.

This retrospective study found 36% of ibrutinib-treated patients, including MCL, developed serious infections, with prior transplant and steroid use identifying a high-risk group needing potential prophylaxis.

Single-cell analysis reveals the HSP90-MYC-CDK9 network drives sequential BTKi and CAR-T resistance, suggesting co-targeting HSP90 and CDK9 as a novel strategy for dual-refractory MCL.